Diuretics
Pharmacology
Katzung
Abnormalities in fluid volume and electrolyte composition are common and important clinical disorders. Drugs that block specific transport functions of the renal tubules are valuable clinical tools in the treatment of these disorders. Although various agents that increase urine volume (diuretics) have been described since antiquity, it was not until 1937 that carbonic anhydrase inhibitors were first described and not until 1957 that a much more useful and powerful diuretic agent (chlorothiazide) became available. Technically, a “diuretic” is an agent that increases urine volume, whereas a “natriuretic” causes an increase in renal sodium excretion and an “aquaretic” increases excretion of solute-free water. Because natriuretics almost always also increase water excretion, they are usually called diuretics. Osmotic diuretics and antidiuretic hormone antagonists (see Agents That Alter Water Excretion) are aquaretics that are not directly natriuretic.
By Dr. Vishal Pawar, MD pharmacology
considering the complex nature of this topic, i am hereby providing a comprehensive review of prostaglandins and its various effects in the body, which after a through go through should be enough for simplifying the understanding of prostaglandins
These are the drugs which antagonize the receptor action of adrenaline and related drugs.
These drugs act by blocking a and/or ß-adrenergic receptors.
α-blockers
PRAZOSIN is a competitive antagonist effective in the management of hypertension. Similar drugs with longer half-lives (e.g. doxazosin, terazosin).
β-blockers
Heart - Decrease heart rate, force of contraction and cardiac output.
Blood Pressure - Decrease in blood pressure (blockage).
Respiratory System – bronchoconstriction.
Eye – Beta-blocking agents reduce intraocular pressure, especially in glaucoma. The mechanism usually reported is decreased aqueous humor production.
Metabolic - Increase LDL and decrease HDL.
Uterus - Relaxation of uterus.
Local anaesthetic - Propranolol has some local anaesthetic action
Diuretics
Pharmacology
Katzung
Abnormalities in fluid volume and electrolyte composition are common and important clinical disorders. Drugs that block specific transport functions of the renal tubules are valuable clinical tools in the treatment of these disorders. Although various agents that increase urine volume (diuretics) have been described since antiquity, it was not until 1937 that carbonic anhydrase inhibitors were first described and not until 1957 that a much more useful and powerful diuretic agent (chlorothiazide) became available. Technically, a “diuretic” is an agent that increases urine volume, whereas a “natriuretic” causes an increase in renal sodium excretion and an “aquaretic” increases excretion of solute-free water. Because natriuretics almost always also increase water excretion, they are usually called diuretics. Osmotic diuretics and antidiuretic hormone antagonists (see Agents That Alter Water Excretion) are aquaretics that are not directly natriuretic.
By Dr. Vishal Pawar, MD pharmacology
considering the complex nature of this topic, i am hereby providing a comprehensive review of prostaglandins and its various effects in the body, which after a through go through should be enough for simplifying the understanding of prostaglandins
These are the drugs which antagonize the receptor action of adrenaline and related drugs.
These drugs act by blocking a and/or ß-adrenergic receptors.
α-blockers
PRAZOSIN is a competitive antagonist effective in the management of hypertension. Similar drugs with longer half-lives (e.g. doxazosin, terazosin).
β-blockers
Heart - Decrease heart rate, force of contraction and cardiac output.
Blood Pressure - Decrease in blood pressure (blockage).
Respiratory System – bronchoconstriction.
Eye – Beta-blocking agents reduce intraocular pressure, especially in glaucoma. The mechanism usually reported is decreased aqueous humor production.
Metabolic - Increase LDL and decrease HDL.
Uterus - Relaxation of uterus.
Local anaesthetic - Propranolol has some local anaesthetic action
ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARB)
Drugs
ACEi include enalapril, ramipril, and lisinopril.
ARBs include losartan and candesartan.
Mechanism
Reduce levels (ACEi) or effects (ARB) of angiotensin II.
Angiotensin II increases BP via systemic vasoconstriction, sodium retention, and aldosterone and ADH release.
Lower efficacy in black patients, so not 1st line in this group.
The medicos PDF app was used to collect this information. I stumbled discovered this amazing app when searching for various slides and books and decided to share it with you all. The Google Play Store has a free version of the app.
measurement of GFR and creatinine clearence-- design of dosage for hepatic patients -- therapeutic drug monitoring and clinical pharmacokinetics fifth pharm D notes
Genetic polymorphism in drug transport and drug targets.pavithra vinayak
Genetic polymorphism in drug transport and targets.--pharmacogenetics
DRUG TRANSPORTER
Two types of transporter :
•ATP binding Cassette (ABC) – Found in ABCB, ABCD and ABCG family. Associated with multidrug resistance (MDR) of tumor cells causing treatment failure in cancer.
•Solute Carrier (SLC) – Transport varieties of solute include both charged or uncharged
P-glycoprotein
• ATP binding cassette subfamily B member- 1 (ABCB 1)
• Multidrug resistance protein 1 (MDR1)
• Transport various molecules, including xenobiotic, across cell membrane
• Extensively distributed and expressed throughout the body
Mechanism of Pglycoprotein
Substrate bind to P-gp form the inner leaflet of the membrane
ATP binds at the inner side of the protein
ATP is hydrolyzed to produce ADP and energy
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)pavithra vinayak
Therapeutic drug monitoring for immunosuppressive agents ( organ transplants)
1)CALCINEURIN INHIBITORS
i. CYCLOSPORIN/ CYCLOSPORINE
ii. SIROLIMUS
iii. TACROLIMUS
iv. EVAROLIMUS
2) ANTIPROLIFERATIVE/ANTIMETABOLIC AGENTS,
i. MYCOPHENOLATE
ii. AZATHIOPRINE
3) BIOLOGICS (ANTIBODIES)
i. MUROMONAB-CD3 (OKT3)
ii. BASILIXIMAB
iii. DACLIZUMAB
iv. ALEMTUZUMAB
v. ANTITHYMOCYTE GLOBULIN
4)GLUCOCORTICOIDS,
clinical pharmacokinetics and therapeutic drug monitoring ----- fifth pharm D notes
conversion from INTRAVENOUS TO ORAL DOSING----- design of dosage regimenpavithra vinayak
conversion from INTRAVENOUS TO ORAL DOSING----- TYPES OF IV TO PO THERAPY CONVERSIONS: MEDICATIONS INCLUDED IN AN IV TO PO CONVERSION PROGRAM: SELECTION OF PATIENTS FOR IV TO PO THERAPY CONVERSION: design of dosage regimen--clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Nomograms and tabulations in design of dosage regimens pavithra vinayak
Nomograms and tabulations in the design of dosage regimens --- NOMOGRAM IN UREMIC PATIENTS: NOMOGRAM FOR RELATIONSHIP BETWEEN CREATININE CLEARANCE AND ELIMINATION RATE CONSTANT FOR FOUR DRUGS clinical pharmacokinetics and therapeutic drug monitoring ---fifth PharmD notes
adaptive methods are doing with feedback in population pharmacokinetics---- clinical pharmacokinetics and therapeutic drug monitoring-- fifth pharm D notes
Bayesian theory in population pharmacokinetics--
1) INTRODUCTION TO BAYESIAN THEORY
2)BAYESIAN PROBABILITY TO DOSING OF DRUGS
3)APPLICATIONS AND USES OF BAYESIAN THEORY IN APPLIED PHARMACOKINETICS:
therapeutic drug monitoring and clinical pharmacokinetics-fifth pharm d notes
depression ,symptoms, mechanism of depression ,classification of antidepressants , tri cyclic anti depressants and its pharmacological actions ,acute poisoning and treatment
introduction ,classification of cholinergic receptor ,and its function ,anti cholinergic agents -atropine and its pharmacology ,semi synthetic and synthetic atropine substitutes
principle action of drugs,types of angina classification of drugs ,nitrates,calcium channel blockers pharmacological actions ,combination therapy and its sid effects
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
4. General effects of α blockers
Blood vessels
α1-blockade→reduces peripheral resistance
Fall in BP
Postural hypotension
α2-blockade in brain ↑se vasomotor tone.
Block pressor action of adrenaline, fall in BP due toβ2.
action- “vasomotor reversal of Dale”
Actions of selective α-agonists supressed.
5. Heart
Reflex tachycardia due to:-
fall in mean arterial pressure
Blockade of presynaptic α2 receptors- ↑ NA release.
Nose: nasal stuffiness
Eye: miosis
GIT: intestinal motility ↑se
Kidney: Hypotension
↓se GFR
NA+ & H2O reabsorption
6. Urinary bladder
α1A blockade- ↓se tone of smooth muscle in trigone,
sphincter & prostrate.
Improved urine flow, used in BPH.
Reproductive system
Contraction of vas deferens result in ejaculation
through α receptors.
Blockade results in impotence.
7. Irreversible non-selective α- blockers
Phenoxybenzamine
Cyclizes spontaneously to highly reactive ethyleniminium
intermediate.
Binds covalently to α-receptors- irreversible or non-
equilibrium competitive block.
Blockade is slow onset & longer duration (3-4 days).
Also inhibits reuptake of NE.
Shifts blood from pulmonary to systemic circuit.
Shift fluid from extravascular to vascular compartment-
relaxation of postcapillary vessels.
8. PK
Preferred ROA- i.v.
Lipid soluble penetrates brain.
Mainly excreted through urine in 24 hrs.
Accumulates in adipose tissue on ch. Administration.
Dose
20-60 mg/d oral
1mg/kg/1hr slow i.v infusion.
Uses
Pheochromocytoma, occasionally 2oshock, PVD.
9. Reversible non-selective α-blockers
Tolazoline
Block is modest & short lasting.
Direct vasodilator & stimulates the heart.
Also blocks 5-HT receptors, histamine like gastric
secretagouge & Ach like motor action on intestine.
SE
N, V, cramps, diarrhoea, nervousness, chills
Tachycardia, Exacerbation of MI, peptic ulcer.
Use
PVD
Pulmonary HT of newborn.
10. Phentolamine
More potent α-blocker than tolazoline.
Other actions are less marked.
Duration of action is shorter (min).
Equally blocks α1 & α2 receptors- NA release ↑sed.
Uses
∆sis & intraop.management of pheochromocytoma.
5mg i.v- B.P falls by 25(D)or35(S)mmHg.
HTN due to clonidine withdrawl, cheese reaction.
Dermal necrosis due to extravasated i.v NA/DA.
Given S.C as local infiltration.
11. Reversible, selective α1- blockers
Prazosin
Highly selective α1-blocker , α1: α2 selectivity 1000:1
Fall in BP with only mild tachycardia.
Dilates arterioles more than veins
Postural hypotension occurs as 1st dose effect, minimized
by starting with low doses at bed time.
Also inhibits PDE- ↑se cAMP in smooth muscle.
PK
Effective orally, BA- 60%.
Highly bound to plasma proteins (α1 acid glycoprotein).
12. Metabolized in liver, 1o excreted in bile.
t1/2 – 2-3hrs, effect lasts for 6-8hrs.
Uses
Primarily as antihypertensive.
LVF not controlled by diuretics & digitalis.
Raynaud’s disease
BPH
Scorpion sting
13. Terazosin &Doxazosin
Long acting( t1/212 & 18hr) congener of prazosin.
Used in HTN & BPH as single daily dose.
Tamsulosin & Silodosin
Uroselective α1A blocker
α1A –bladder base, prostrate. α1B- blood vessels.
Don't cause significant changes in BP & HR.
t1/2- 6-9hr, MR cap(0.2-0.4 mg) can be taken OD.
Efficacious in Rx of BPH.
SE: retrograde ejaculation, dizziness,, floppy iris syd.
Silodosin weaker(4-8mg/d) but longer acting.
14. Bunazosin & Alfuzosin
Orally effective α1 blockers similar to prazosin.
Alfuzosin t1/2 4hrs (2.5mgTDS or 10mg SR OD).
CI in hepatic impairment, metabolized in liver.
Bunazosin slightly longer t1/2.
Primarily used in BPH.
15. α2-receptor blockers
Yohimbine
Natural alkaloid from Pausinystalia yohimbe.
No established clinical role.
Idazoxan
Has membrane stabilizing action.
Ergot alkaloids
Ergotamine & Dihydroergotamine
Competitive α-receptor blockers.
Principal use is migraine.
16. Uses of α-Blockers
Pheochromocytoma
Tumor of adrenal medullary cells-excess Cas.
Cause intermittent or persistent hypertension.
Diagnosed by- ↑se urinary VMA, normetanephrine.
phentolamine test can also be performed.
Rx
Phenoxybenzamine
Definitive therapy for inoperable or malig.tumors.
Preoperative- orally x 2wks, i.v during surgery as-
17. 1. Normalizes blood volume & body H2O distribution.
2. During surgery excess release of CAs in to blood.
Phentolamine drip can also be used.
Hypertension
Selective α1 blocker prazosin is preferred.
2o shock
Fluid loss leads to vasoconstriction.
Should not be given without fluid replacement.
18. Peripheral vascular disease
Little benefit in Buerger’s disease & int.claudication.
More useful in Reynaud's disease & acrocyanosis
where vasoconstriction is prominent.
Prazosin or phenoxybenzamine are useful.
CHF
Short term benefit, leads to Na+ & H2O retension.
Migraine
Ergotamine more effective
19. Benign prostrate hypertrophy
Two classes of drugs are available.
1. α1-blockers- ↓ tone of prostrate and bladder neck.
2. 5-α reductase inhibitors: finasteride & dutasteride.
arrest growth/reduce size of prostrate.
α1-blockers gives faster and greater symptomatic
releif than finasteride.
Effect of α1-blockers decline after several years of
use, must be combined with fiasteride.
Terazosin, doxazosin, tamsulosin are preferred.
20.
21.
22. Side effects of α-blockers
Palpitation
Postural hypotension
Nasal blockade
Diarrhea
Fluid retention
Inhibition of ejaculation & impotence.